Natural killer cells (hereinafter sometimes referred to as "NK cells") are large granular lymphocytes ("LGLs") comprising 2-15% of peripheral blood mononuclear cells in healthy individuals. Although NK cells do not rearrange or express either of the known T cell receptor complexes, they can recognize and kill certain virus-infected and transformed cells in a non-MHC-restricted fashion, without prior sensitization. With the exception of CD16, an Fc receptor for immunoglobulin that recognizes antibody-coated target cells, the NK cell surface receptors responsible for target cell recognition have not been identified. The lack of a defining surface receptor requires NK cells to be identified by a combination of phenotypic and functional characteristics.
Although most NE cells are CD3:TCR-, CD16+, CD56+ LGLs, there is considerable phenotypic and functional heterogeneity within this population (Trinchieri, Adv. Immunol., 47:187 (1989)). For example, the surface density of CD56 has been shown to define functionally distinct NK cell populations. CD56.sup.bright NK cells are largely CD16.sup.+, agranular lymphocytes deficient in cytolytic effector function that proliferate vigorously in response to exogenous IL-2. CD56.sup.dim NK cells are CD16.sup.+ LGLs possessing potent cytolytic effector function that do not proliferate in response to IL-2. Because some T cells express both CD16 and CD56, these molecules, by themselves, cannot define the NK cell population. (Trinchieri, 1989). Furthermore, because the expression of CD56 on the functionally differentiated population of NK cells is low, monoclonal antibodies reactive with CD56 cannot be used to reliably distinguish this subpopulation of NK cells from other cells in a sample.
It is an object of the present invention to identify a novel cell surface structure that is preferentially expressed on functionally differentiated natural killer cells, which can be used to reliably identify this subpopulation of peripheral blood mononuclear cells.
It is another object of the invention to provide antibodies that will bind to unique epitopes present on a cell surface structure selectively expressed on functionally differentiated NK cells.